Remotely controlled chemomagnetic modulation of targeted neural circuits
Remotely controlled chemomagnetic modulation of targeted neural circuits
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DOI：
10.1038/s41565-019-0521-z
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发表时间：
2019-10-01
影响因子：
38.3
通讯作者：
Anikeeva, Polina
中科院分区：
文献类型：
--
作者：
Rao, Siyuan;Chen, Ritchie;Anikeeva, Polina
将神经回路输出与行为联系起来可以通过对特定细胞群的精确化学操作来促进（1，2）。由设计师小分子专门激活的工程受体能够操纵特定的神经通路（3，4）。然而，到目前为止，它们在行为研究中的应用受到全身注射的低时间分辨率与植入插管或输液泵的侵入性之间的权衡的阻碍（2）。在这里，我们开发了一种远程控制的化学磁调制-一种基于纳米材料的技术，允许在自由移动的受试者中对目标神经群体进行药理学询问。在交变磁场（AMF）存在下由磁性纳米颗粒（MNP）耗散的热触发小分子从热敏脂质囊泡释放，具有20 s的潜伏期。再加上工程受体的化学发生激活，这种技术允许控制特定的神经元的时间和空间精度。将化学磁性颗粒递送到腹侧被盖区（VTA）允许远程调节小鼠的动机行为。此外，这种化学磁性方法通过使受体配体的调节释放激活内源性回路。将化学磁调制应用于中脑核（NAc）中的内源性多巴胺受体D1（DRD 1）激动剂，该脑区参与介导社会互动，从而增加小鼠的社交能力。通过对神经元中特定的配体-受体相互作用提供时间上精确的控制，这种方法可以促进行为生物体中的分子神经科学研究。
Connecting neural circuit output to behaviour can be facilitated by the precise chemical manipulation of specific cell populations(1,2). Engineered receptors exclusively activated by designer small molecules enable manipulation of specific neural pathways(3,4). However, their application to studies of behaviour has thus far been hampered by a trade-off between the low temporal resolution of systemic injection versus the invasiveness of implanted cannulae or infusion pumps(2). Here, we developed a remotely controlled chemomagnetic modulation-a nanomaterials-based technique that permits the pharmacological interrogation of targeted neural populations in freely moving subjects. The heat dissipated by magnetic nanoparticles (MNPs) in the presence of alternating magnetic fields (AMFs) triggers small-molecule release from thermally sensitive lipid vesicles with a 20 s latency. Coupled with the chemogenetic activation of engineered receptors, this technique permits the control of specific neurons with temporal and spatial precision. The delivery of chemomagnetic particles to the ventral tegmental area (VTA) allows the remote modulation of motivated behaviour in mice. Furthermore, this chemomagnetic approach activates endogenous circuits by enabling the regulated release of receptor ligands. Applied to an endogenous dopamine receptor D1 (DRD1) agonist in the nucleus accumbens (NAc), a brain area involved in mediating social interactions, chemomagnetic modulation increases sociability in mice. By offering a temporally precise control of specified ligand-receptor interactions in neurons, this approach may facilitate molecular neuroscience studies in behaving organisms.